Document Type : Systematic Review


1 Department of Infectious Diseases and Tropical Medicine, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

3 Viro-immunology Research Unit, Department of Infectious Disease, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

4 Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

5 Department of Parasitology and Mycology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

6 Department of Internal Medicine, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran

7 Department of Infectious Diseases, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

8 Department of Medical Microbiology and Parasitology, College of Health Sciences, Bayero University, Kano, Nigeria

9 Department of Pathology, School of Medicine, Imam Khomeini Hospital Tehran University of Medical Sciences, Tehran, Iran

10 Department of Infectious Diseases, Alborz University of Medical Sciences, Karaj, Iran

11 Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran

12 Department of Infectious Diseases, Arak Social Security Organization Hospital, Arak, Iran

13 Neurocognitive Science special Linguistics, Institute for Cognitive Science Studies, Tehran, Iran

14 Infectious Disease and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran


Cerebral mucormycosis (CM) is a life-threatening manifestation of mucormycosis, an angioinvasive fungal infection caused by Mucorales. We sought to systematically review all available case reports to describe epidemiologic features, clinical manifestations, predisposing factors, and diagnostic and treatment strategies of CM. A systematic search was conducted using a combination of the following keywords: "Mucor", "Zygomycetes", "mucormycosis", "cereb*", "brain", "central nervous system", and "intracranial", separately and in combination until  December 31st 2018. Data sources included  PubMed, Scopus, EMBASE, Web of Science, Science Direct, and Proquest without limiting the time of publication. We included 287 articles corresponding to 345 cases of CM. Out of the 345 cases, 206 (60%) were male with a median age of 44 years; 130 (38%) were reported from North America; 87 (25%) from Asia; and 84 (24%) from Europe. The median time from onset of symptoms to presentation was 3-7 days (65/345, 65%). The highest mortality was observed among patients with diabetes mellitus (P=0.003). Debridement of infected brain tissue was associated with improved survival in CM cases (OR 1.5; 95% CI 01.3-1.8; P<0.0001). The use of liposomal amphotericin B (L-AMB) was significantly associated with patients' recovery (OR 2.09; 95% CI 1.2-3.4; P=0.003). The combination of L-AMB and posaconazole (12.5%) was more effective than the monotherapy treatment of CM cases (P=0.009). Clinicians should consider DM as an important risk factor for CM. Moreover, surgical debridement and antifungal combination therapy could be an effective approach in the management of CM patients.


  • A set of 287 articles containing 345 cases of cerebral mucormycosis were included.
  • Diabetes mellitus without ketoacidosis (n=176, 51%) followed by hematological malignancy or hematopoietic stem cell transplantation (n=80, 23.2%) were the most common underlying conditions.
  • Orbital symptoms (n=160, 46.3%) and neurological symptoms (n=142, 41%) were the most common symptoms.
  • Multiple cerebral lobes (n=100, 28.9%) and temporal lobe (n=54, 15.6%) were the most common pattern of involvement.
  • Regarding the outcome, 136 (39.4%) of 345 patients died.


Main Subjects

  1. Kennedy KJ, Daveson K, Slavin MA, van Hal SJ, Sorrell TC, Lee A, et al. Mucormycosis in Australia: contemporary epidemiology and outcomes. Clin Microbiol Infect. 2016;22(9):775-81. [DOI:10.1016/j.cmi.2016.01.005] [PMID]
  2. Bitar D, Van Cauteren D, Lanternier F, Dannaoui E, Che D, Dromer F, et al. Increasing incidence of zygomycosis (mucormycosis), France, 1997-2006. Emerg Infect Dis. 2009;15(9):1395. [PMCID] [DOI:10.3201/eid1509.090334] [PMID]
  3. Kontoyiannis DP, Azie N, Franks B, Horn DL. Prospective antifungal therapy (PATH) alliance®: focus on mucormycosis. Mycoses. 2014;57(4):240-6. [DOI:10.1111/myc.12149] [PMID]
  4. Roden MM, Zaoutis TE, Buchanan WL, Knudsen TA, Sarkisova TA, Schaufele RL, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41(5):634-53. [DOI:10.1086/432579] [PMID]
  5. Skiada A, Pagano L, Groll A, Zimmerli S, Dupont B, Lagrou K, et al. Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin Microbiol Infect. 2011;17(12):1859-67. [DOI:10.1111/j.1469-0691.2010.03456.x] [PMID]
  6. Francis JR, Villanueva P, Bryant P, Blyth CC. Mucormycosis in children: review and recommendations for management. J Pediatric Infect Dis Soc. 2017;7(2):159-64. [DOI:10.1093/jpids/pix107] [PMID]
  7. Singh N, Aguado JM, Bonatti H, Forrest G, Gupta KL, Safdar N, et al. Zygomycosis in solid organ transplant recipients: a prospective, matched case-control study to assess risks for disease and outcome. J Infect Dis. 2009;200(6):1002-11. [DOI:10.1086/605445] [PMID]
  8. Robin C, Alanio A, Cordonnier C. Mucormycosis: a new concern in the transplant ward? Curr Opin Hematol. 2014;21(6):482-90. [PMID] [DOI:10.1097/MOH.0000000000000082]
  9. Gamaletsou MN, Sipsas NV, Roilides E, Walsh TJ. Rhino-orbital-cerebral mucormycosis. Curr Infect Dis Rep. 2012;14(4):423-34. [DOI:10.1007/s11908-012-0272-6] [PMID]
  10. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264-9. [PMID] [DOI:10.7326/0003-4819-151-4-200908180-00135]
  11. Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147(8):573-7. [PMID] [DOI:10.7326/0003-4819-147-8-200710160-00010]
  12. Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis. 2012;54 Suppl 1(suppl_1):S23-34. [DOI:10.1093/cid/cir866] [PMID]
  13. Kerezoudis P, Watts CR, Bydon M, Dababneh AS, Deyo CN, Frye JM, et al. Diagnosis and Treatment of Isolated Cerebral Mucormycosis: Patient-Level Data Meta-Analysis and Mayo Clinic Experience. World Neurosurg. 2019;123:425-34 e5. [DOI:10.1016/j.wneu.2018.10.218] [PMID]
  14. Jeong W, Keighley C, Wolfe R, Lee WL, Slavin MA, Kong DCM, et al. The epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports. Clin Microbiol Infect. 2019;25(1):26-34. [DOI:10.1016/j.cmi.2018.07.011] [PMID]
  15. Katragkou A, Walsh TJ, Roilides E. Why is mucormycosis more difficult to cure than more common mycoses? Clin Microbiol Infect. 2014;20 Suppl 6:74-81. [DOI:10.1111/1469-0691.12466] [PMID]
  16. Cornely OA, Alastruey-Izquierdo A, Arenz D, Chen SCA, Dannaoui E, Hochhegger B, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis. 2019;19(12):e405-e21.
  17. Otto WR, Pahud BA, Yin DE. Pediatric Mucormycosis: A 10-Year Systematic Review of Reported Cases and Review of the Literature. J Pediatric Infect Dis Soc. 2019;8(4):342-50. [DOI:10.1093/jpids/piz007] [PMID]
  18. Kursun E, Turunc T, Demiroglu YZ, Aliskan HE, Arslan AH. Evaluation of 28 cases of mucormycosis. Mycoses. 2015;58(2):82-7. [DOI:10.1111/myc.12278] [PMID]
  19. Chikley A, Ben-Ami R, Kontoyiannis DP. Mucormycosis of the Central Nervous System. J Fungi (Basel). 2019;5(3):59. [DOI:10.3390/jof5030059] [PMID] [PMCID]
  20. Zaoutis TE, Roilides E, Chiou CC, Buchanan WL, Knudsen TA, Sarkisova TA, et al. Zygomycosis in children: a systematic review and analysis of reported cases. Pediatr Infect Dis J. 2007;26(8): 723-7. [DOI:10.1097/INF.0b013e318062115c] [PMID]